Progressive Cognitive Deficits in a Mouse Model of Recurrent Photothrombotic Stroke

Abstract

Focal cerebral ischemia was induced in the right parietal cortex of 25 adult male C57BL/6 mice by photothrombosis of cortical microvessels (detailed Methods are available in the online-only Data Supplement).6 At an interval of 10 days, a second photothromboticBackground and Purpose-In spite of its high disease burden, there is no specific treatment for multi-infarct dementia. The preclinical evaluation of candidate drugs is limited because an appropriate animal model is lacking. Therefore, we aimed to evaluate whether a mouse model of recurrent photothrombotic stroke is suitable for the preclinical investigation of multi-infarct dementia. Methods-Recurrent photothrombotic cortical infarcts were induced in 25 adult C57BL/6 mice. Twenty-five sham-operated animals served as controls. The object recognition test and the Morris water maze test were performed >6 weeks to assess cognitive deficits. Afterward, histological analyses were performed to characterize histopathologic changes associated with recurrent photothrombotic infarcts. Results-After the first infarct, the object recognition test showed a trend toward an impaired formation of recognition memories (P=0.08), and the Morris Water Maze test revealed significantly impaired spatial learning and memory functions (P<0.05). After recurrent infarcts, the object recognition test showed significant recognition memory deficits (P<0.001) and the Morris water maze test demonstrated persisting spatial learning and memory deficits (P<0.05). Histological analyses revealed remote astrogliosis in the hippocampus. Conclusions-Our results show progressive cognitive deficits in a mouse model of recurrent photothrombotic stroke. The presented model resembles the clinical features of human multi-infarct dementia and enables the investigation of its pathophysiological mechanisms and the evaluation of treatment strategies.

More than motor impairment: A spatiotemporal analysis of cognitive impairment and associated neuropathological changes following cortical photothrombotic stroke

“…27 Further, this photothrombotic stroke model has been reported to elicit long-term deficits in learning and memory, as assessed by the Morris water maze. 49 Critically, given that stroke affects a range of cognitive domains, and these effects are known to be persistent long-term, we sought to further understand the devastating effects of stroke on cognition, by using a mouse touchscreen platform. 50 This mouse touchscreen platform is recognised to avoid some of the limitations associated with classical assessments.…”

Rebuilding hippocampus neural circuit with hADSC-derived neuron cells for treating ischemic stroke

“…To evaluate the effect of hADSC-NCs on mouse spatial learning and memory, a Morris water maze equipped with a digital camera was used to determine the physiological indexes for the poststroke mice. The general protocols were similar to those previously published with minor modifications [ 12 , 53 ]. The Morris test program consisted of 5 days of training plus 1 final test day.…”

Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke

“…There are several other ways to induce focal ischemia including the photothrombotic (Schmidt et al , 2015), autologous clot (Jin et al , 2014; Taupin and Gage, 2002), and endothelin-1 (Roome et al , 2014) methods (Table 1). The photothrombotic method is a non-invasive method in which a photosensitive dye is intravenously injected into the animal (Chen et al , 2004; De Ryck et al , 1996; Eichenbaum et al , 2002).…”